Summary Immunotherapy is a promising area of therapy in patients with neuro-oncological malignancies. However, early-phase studies show unique challenges associated with the assessment of ...radiological changes in response to immunotherapy reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumour regression, can still occur after initial disease progression or after the appearance of new lesions. Refinement of the response assessment criteria for patients with neuro-oncological malignancies undergoing immunotherapy is therefore warranted. Herein, a multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describe immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria based on guidance for the determination of tumour progression outlined by the immune-related response criteria and the RANO working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease within 6 months of initiating immunotherapy, including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for the use of corticosteroids. We review the role of advanced imaging techniques and the role of measurement of clinical benefit endpoints including neurological and immunological functions. The iRANO guidelines put forth in this Review will evolve successively to improve their usefulness as further experience from immunotherapy trials in neuro-oncology accumulate.
Immunotherapy has been highlighted because we have obtained much evidence, which includes theoretical backborn as well as favorable results from clinical trials. As immunotherapy gives an apparently ...different cytotoxic mechanism and a little adverse event, the promising results are getting a lot of attention. In this article, cancer immunotherapy for gliomas is reviewed thoroughly from the literature, focusing on the clinical trial results.
Studies regarding hematoma stiffness and removal difficulty are scarce. This study explored the association between hematoma stiffness and surgical results of endoscopic hematoma removal for ...intracerebral hemorrhage. It also aimed to clarify factors associated with hematoma stiffness. We classified intracerebral hematoma as either soft or firm stiffness by retrospectively evaluating operative videos by two neurosurgeons. The interobserver reliability of the classification was assessed by calculating the κ values. We investigated the relationship between hematoma stiffness and surgical results. Favorable hematoma removal (FHR) was defined as a residual hematoma volume of ≤15 mL or removal rate of ≥70%. Furthermore, we compared the background characteristics, imaging findings, and laboratory data between the two groups. Forty patients were included in this study. The mean baseline hematoma volume was 69.9 mL (range, 41.3-97.6 mL). FHR was accomplished in 35 cases (87.5%). Thirty-four patients (85%) were in the soft hematoma group (group S). Six patients (15%) were in the firm hematoma group (group F). Classification of hematoma stiffness demonstrated an excellent degree of interobserver agreement (κ score = 0.91). Patients in group S had a high FHR rate (p = 0.018) and short endoscopic procedure times (p = 0.00034). The island sign was present in group S (p = 0.030). Patients in group F had significantly high fibrinogen levels (p = 0.049) and low serum total calcium (p = 0.032), hemoglobin (p = 0.041), and hematocrit (p = 0.011) levels. Hematoma stiffness during endoscopic surgery for intracerebral hemorrhage correlates with surgical results, including the endoscopic procedure time and accomplishing rate of FHR.
Oral care for critically ill patients helps provide comfort and prevent ventilator-associated pneumonia. However, a standardized protocol for oral care in intensive care units is currently ...unavailable. Thus, this study aimed to determine the overall oral care practices, including those for intubated patients, in Japanese intensive care units. We also discuss the differences in oral care methods between Japanese ICUs and ICUs in other countries. This study included all Japanese intensive care units meeting the authorities' standard set criteria, with a minimum of 0.5 nurses per patient at all times and admission of adult patients requiring mechanical ventilation. An online survey was used to collect data. Survey responses were obtained from one representative nurse per intensive care unit. Frequency analysis was performed, and the percentage of each response was calculated. A total of 609 hospitals and 717 intensive care units nationwide participated; among these, responses were collected from 247 intensive care units (34.4%). Of these, 215 (87.0%) and 32 (13.0%) reported standardized and non-standardized oral care, respectively. Subsequently, the data from 215 intensive care units that provided standardized oral care were analyzed in detail. The most common frequency of practicing oral care was three times a day (68.8%). Moreover, many intensive care units provided care at unequal intervals (79.5%), mainly in the morning, daytime, and evening. Regarding oral care methods, 96 (44.7%) respondents used only a toothbrush, while 116 (54.0%) used both a toothbrush and a non-brushing method. The findings of our study reveal current oral care practices in ICUs in Japan. In particular, most ICUs provide oral care three times a day at unequal intervals, and almost all use toothbrushes as a common tool for oral care. The results suggest that some oral care practices in Japanese ICUs differ from those in ICUs in other countries.
Introduction
This study investigated the extent of contamination with antineoplastic agents on floor surfaces of the ward and the outpatient chemotherapy center of a Japanese cancer center to ...evaluate healthcare workers’ risk of occupational exposure to antineoplastic agents outside of the designated drug preparation areas.
Methods
In this study conducted at Aichi Cancer Center, the amount of fluorouracil detected on various floor surfaces was measured using liquid chromatography—tandem quadrupole mass spectrometry. Areas around the toilets were cleaned with a surfactant two or three times a day, whereas other floor surfaces were cleaned only with dry and wet mops.
Results
Fluorouracil was detected on all surveyed floor surfaces, with particularly high amounts detected around the toilet areas in the ward. Additionally, areas with more human traffic tended to have higher fluorouracil contamination.
Conclusions
This survey suggested that antineoplastic agent contamination occurring through patient excretions might spread throughout the hospital with human traffic. Therefore, controlling the spread of antineoplastic agent contamination in hospitals should include the review of measures to mitigate contamination around toilets and to implement effective cleaning methods for floor surfaces.
Maneuvering motions of a ship in calm water are studied through the concept of MMG model. Governing forces are defined by the use of available empirical formulae that require only main ship ...particulars as input variables. In order to validate the calculation tool, a full-scale sea experiment was carried out in Osaka Bay using a 17-m twin-screw passenger ferry. Test execution and data measurement were performed through the utilization of an autopilot control unit and satellite compass. The result of a straight running test confirms the acceptable accuracy in addressing the surge motion problem. Reasonable agreement between simulation and experiment is also confirmed for 5∘/5∘ and 10∘/10∘ zig-zag tests despite the strong environmental disturbance. The current model can generally represent the subject ship maneuvering motions and is promising for the application to other ship hulls.
Intracranial germinomas mainly arise in the pineal gland or neurohypophyseal region. The basal ganglia have been reported as the site of occurrence for ectopic germinomas, whereas other sites have ...been rarely described. We experienced a case of multifocal ectopic germinoma that arose in the septum pellucidum and the dorsal brain stem, not including the pineal gland, neurohypophysis, and basal ganglia of ectopic germinoma in a pregnant woman.
The patient initially presented to our institution with complaints of diplopia in the past 14 weeks of gestation, and imaging later revealed two intracranial neoplastic lesions, with one lesion involving the septum pellucidum and the other involving the dorsal brainstem. Both tumors were partially excised via a transcortical approach. Based on the results of pathology and immunohistochemistry, the patient was diagnosed with germinoma, and the intraoperative spinal fluid cytology was class V in Papanicolaou classification. The patient received three courses of ifosfamide, carboplatin, and etoposide together with whole-brain irradiation, which resulted in complete elimination of the tumors. No evidence of recurrence was identified after 18 months.
The results illustrated the need to consider germinoma in the differential diagnosis if the lesions involve midline structures such as the septum pellucidum or dorsal brainstem. Given the rarity of germinoma arising outside the pineal gland and neurohypophyseal region, these findings provide key insights into the diagnosis and treatment of this disease.
Primary central nervous system lymphoma (PCNSL), a relatively rare brain tumor, bears a dire prognosis. On occasion, the rapid progression of the tumor makes immediate diagnosis and initiation of ...therapy imperative. To achieve swift diagnosis, we adopt flow cytometry (FCM) in addition to conventional histopathology. This study aimed to reveal the utility of FCM diagnosis for PCNSL and the cause of false-negative results of FCM diagnosis. We investigated 33 patients with suspected PCNSL on neuroradiological findings and received both FCM and histological diagnosis. The patients' electronic medical records were investigated, and histological findings, results of FCM, and other clinical data were evaluated. Overall, 27 patients (14 males and 13 females) were diagnosed with PCNSL by histological confirmation. The median age at diagnosis was 68 years. FCM analysis showed lymphoma pattern in 24 cases; however, FCM results did not show lymphoma pattern (sensitivity: 88.9%, specificity: 100%) in the other three lymphoma cases (FCM discordant: FCM-D) and six nonlymphomatous tumor cases. Analysis of FCM-D cases showed the infiltration of T lymphocytes or astrocytes into the tumor tissue, indicating tumor microenvironmental reaction; it is assumed that these reactions deceived FCM diagnosis. The survival of FCM-D patients was superior to FCM concordant counterpart, although the difference was not significant (p = 0.459). The diagnosis of PCNSL by FCM is rapid and highly reliable. Some FCM-D cases are PCNSLs with strong tumor microenvironmental reactions.
Purpose
The safety and clinical efficacy of WT1 human leukocyte antigen (HLA) class I peptide vaccine have been established, but the safety of a cocktail vaccine of WT1 HLA class I and II peptides ...has not. To verify its safety, we performed a phase I clinical trial for patients with recurrent malignant gliomas and assessed the immunological responses and survival data.
Patients and methods
Fourteen HLA-A*24:02-positive patients with recurrent malignant glioma (2 with grade 3, 12 with grade 4) were enrolled. Every week, the patients received alternately a vaccine containing 3 mg of WT1 HLA-A*24:02-restricted (HLA class I) peptide and a cocktail vaccine of the HLA class I peptide and one of 0.75, 1.5 or 3 mg of the WT1 HLA class II peptide. For patients who showed no significant adverse effects within 6 weeks, the WT1 vaccine was continued at 2–4-week intervals.
Results
Eleven of the 14 patients completed WT1 vaccination for 6 weeks, while 3 patients dropped out earlier due to disease progression. All patients showed grade I level of skin disorders at the injection sites. No grade III/IV toxicity or dose-limiting toxicity was observed for any dose of WT1 HLA class II peptide. Six of the 14 patients had stable disease at 6 weeks. Median OS and 1-year OS rates were 24.7 weeks and 36%, respectively.
Conclusion
The safety of a cocktail vaccine of WT1 HLA class I and II peptides for malignant gliomas was verified. This vaccine is, therefore, considered promising for patients with recurrent malignant glioma.
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